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鉴定 ITGB 超家族成员在胰腺癌中的预后和肿瘤学价值。

Characterization of the prognostic and oncologic values of ITGB superfamily members in pancreatic cancer.

机构信息

Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Shantou University of Medical College, Shantou, China.

出版信息

J Cell Mol Med. 2020 Nov;24(22):13481-13493. doi: 10.1111/jcmm.15990. Epub 2020 Oct 18.

DOI:10.1111/jcmm.15990
PMID:33073486
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7701563/
Abstract

Integrin β (ITGB) superfamily members have been reported to play important roles in multiple biological functions in various cancers. However, the prognostic and oncologic values of ITGB superfamily members have not been systematically investigated in pancreatic cancer (PC). In this study, the mRNA expression and biological functions of ITGB superfamily members in PC were evaluated by bioinformatic analysis. Our results demonstrated that ITGB1, ITGB4, ITGB5 and ITGB6 overexpressions were significantly associated with advanced AJCC stage and histologic grade, and worse prognosis in PC. A prognostic signature based on ITGB1, ITGB4, ITGB5 and ITGB6 showed a reliable predictive performance. Furthermore, one CpGs (cg20545410) in promoter region of ITGB1, four (cg18709893, cg15700850, cg20667796 and cg18326022) of ITGB4, two (cg10977398 and cg03518058) of ITGB5 and one (cg23008083) of ITGB6 were negatively associated with their corresponding mRNA expression, and positively associated with prognosis in PC. We also identified TFAP2A as the potential transcription factor for ITGB4, SP1 for ITGB1 and ITGB6, and FHL2 for ITGB5 and ITGB6. ITGB1, ITGB4, ITGB5 and ITGB6 overexpressions were all significantly involved in focal adhesion signalling pathway. ITGB1 and ITGB5 overexpressions also associated with up-regulation of TGF-β and WNT signalling pathway, whereas ITGB4 and ITGB6 overexpressions associated with up-regulation of Notch signalling pathway. Besides, ITGB1, ITGB5 and ITGB6 overexpressions significantly correlated with immunosuppression in PC. In summary, our study investigated the multilevel prognostic and biological values of ITGB superfamily members in PC.

摘要

整合素β（ITGB）超家族成员已被报道在多种癌症的多种生物学功能中发挥重要作用。然而，ITGB 超家族成员在胰腺癌（PC）中的预后和肿瘤学价值尚未得到系统研究。在这项研究中，通过生物信息学分析评估了 ITGB 超家族成员在 PC 中的 mRNA 表达和生物学功能。我们的结果表明，ITGB1、ITGB4、ITGB5 和 ITGB6 的过表达与 PC 中 AJCC 晚期分期和组织学分级以及更差的预后显著相关。基于 ITGB1、ITGB4、ITGB5 和 ITGB6 的预后标志物显示出可靠的预测性能。此外，ITGB1 启动子区域的一个 CpGs（cg20545410）、ITGB4 的四个（cg18709893、cg15700850、cg20667796 和 cg18326022）、ITGB5 的两个（cg10977398 和 cg03518058）和 ITGB6 的一个（cg23008083）与相应的 mRNA 表达呈负相关，与 PC 中的预后呈正相关。我们还确定 TFAP2A 为 ITGB4 的潜在转录因子，SP1 为 ITGB1 和 ITGB6，FHL2 为 ITGB5 和 ITGB6。ITGB1、ITGB4、ITGB5 和 ITGB6 的过表达均显著参与粘着斑信号通路。ITGB1 和 ITGB5 的过表达也与 TGF-β和 WNT 信号通路的上调相关，而 ITGB4 和 ITGB6 的过表达与 Notch 信号通路的上调相关。此外，ITGB1、ITGB5 和 ITGB6 的过表达与 PC 中的免疫抑制显著相关。总之，我们的研究调查了 ITGB 超家族成员在 PC 中的多层次预后和生物学价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f07/7701563/cdaed76dd9fc/JCMM-24-13481-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f07/7701563/e9bacce96505/JCMM-24-13481-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f07/7701563/bceb1593e994/JCMM-24-13481-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f07/7701563/164b80643d16/JCMM-24-13481-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f07/7701563/4ee2d3560510/JCMM-24-13481-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f07/7701563/8fbaaab6c958/JCMM-24-13481-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f07/7701563/cd54ce587ac9/JCMM-24-13481-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f07/7701563/cdaed76dd9fc/JCMM-24-13481-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f07/7701563/e9bacce96505/JCMM-24-13481-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f07/7701563/bceb1593e994/JCMM-24-13481-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f07/7701563/ddbf72d5c9d3/JCMM-24-13481-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f07/7701563/aaa0b87e648c/JCMM-24-13481-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f07/7701563/164b80643d16/JCMM-24-13481-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f07/7701563/4ee2d3560510/JCMM-24-13481-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f07/7701563/8fbaaab6c958/JCMM-24-13481-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f07/7701563/cd54ce587ac9/JCMM-24-13481-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f07/7701563/cdaed76dd9fc/JCMM-24-13481-g009.jpg

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